Will Serious CR Beat a Healthy, Obesity-Avoiding Diet & Lifestyle?

[Dean Pomerleau]

Gordo,

 

That reminds me, you should edit the wikipedia page on calorie restriction, it seems quite dated.

 

You've got to be kidding me. Are you trying to undermine my resolve Gordo!? You're like tempting a junkie with one more fix...

 

Yes, having just read the CR Wikipedia page, ironically for the first time, it does seem a bit overly optimistic and could use some sprucing up. But overall I doesn't look that bad to me. The opening paragraph isn't too wrong in its claims:

 

Calorie restriction without malnutrition has been shown to work in a variety of species, among them yeast, fish, rodents and dogs to decelerate the biological aging process, resulting in longer maintenance of youthful health and an increase in both median and maximum lifespan.^[1] The life-extending effect of calorie restriction however is not shown to be universal.^[2]

 

At least it doesn't include cows or primates in its list of species that have been shown <sic> to benefit. Sure I could bash on the evidence for rodents and dogs, as I've done all over the place in this very thread (start with the opening post) and it's plethora of web of links. But at least it includes the caveat about CR's lack of universality. 

 

Granted it's got a hole you could drive a truck through in the second paragraph relating to the monkey trial(s) (my emphasis throughout):

 

One, begun in 1987 by the National Institute on Aging, published interim results in August 2012 indicating that CR confers health benefits in these animals, but did not demonstrate increased median lifespan; maximum lifespan data are not yet available, as the study is still ongoing.

 

Are they serious? That is one optimistic spin, to put it mildly. Mr. Optimism himself (who shall remain nameless and free from my pejorative aspersions if I .. can ... keep .... myself ..... in ......check, and who penned an amazing blog post critiquing the CR primate results), quotes from the same 2012 NIA study the Wikipedia page is referencing, were the authors say:

 

Considering that just less than 50% of young monkeys are still alive, these data do not represent final lifespan curves in this study. On the basis of lifespan projections using the hazard function, most animals are projected to be dead 10 years from now and the estimated probability statistics indicates a likelihood of less than 0.1% chance that the overall survival outcome would favour the CR group. The probability that a significantly different effect on mean survival will emerge in the next 5–10 years of the study is very low; however, a potential effect on maximum lifespan can not be ruled out.[1]

 

Hmmm... Less than 0.1% chance that the overall survival outcome would favor the CR group.  In that light, the Wiki entry seems a bit optimistic to me. Anyone else?

 

Perhaps it's easier to judge from a picture. Here are the all-cause (left) and age-related (right) survival curves for the NIA monkeys with CR groups in blue, controls in red, males as solid lines, females as dashed lines:

 

Figure 3: Kaplan‐Meier survival curves for (a) all-cause and (b) age-related mortality for pooled (young- and old-onset)

monkeys in the NIA study. Reproduced from ([1], Supplementary Information).

 

Notice anything? All the within-sex curves are freakin' indistinguishable! Am I missing something? Does anyone else happen to notice that the emperor have no freakin' clothes?!

 

See any hope of a significant (let alone meaningful, to say nothing of dramatic) advantage for the CR monkeys relative to controls who were fed a healthy diet? Me neither. So much for "maximum lifespan data are not yet available, as the study is still ongoing."

 

Sure, you can check out Mr. Nameless' blog post on the topic, which overall is admirably tempered in its enthusiasm, but which nonetheless offers some pretty fancy bobbing and weaving in an attempt to preserve a sliver of hope for those still-delusional folks who refuse to believe that for humans at least, serious CR won't work better than a healthy, obesity-avoiding diet and lifestyle.

 

To its credit, and similarly to Nameless' blog post, the section of the CR Wikipedia entry specifically discussing effects in primates, does say something rational to explain the failure of the NIA CR monkeys to live longer:

 

One hypothesis is that the animal's genetics and the quality of the food are more important than the quantity.

 

Further, in the section on humans it says:

 

Another objection to CR as an advisable lifestyle for humans is the claim that the physiological mechanisms that determine longevity are very complex, and the effect would be small to negligible in our species.

 

And the entry does have sections on Concerns and Confounders and Health Effects where many of the problems (and the benefits) we discuss around here are touched on. The downsides they touch on but done elaborate or emphasize, including bone issues / osteoporosis, muscle loss / sarcopenia, malnutrition, cold sensitivity, and anemia, just to name a few. They do a pretty good job on the CR gotcha's, but there is a glaring omission that over the years has really bitten at least one old-timer who I love dearly but who I nonetheless bashed on recently to help make the point, namely that CR impairs wound healing and seriously undermines one's ability to fight (off) established infections.

 

It also does a terrible job with the connection between CR and cold exposure:

 

Caloric restriction lowers the core body temperature, a phenomenon believed to be an adaptive response to reduce energy expenditure when nutrients availability is limited. Lowering the temperature may prolong the lifespan of cold blooded animals. Mice, which are warm blooded, have been engineered to have a reduced core body temperature which increased the lifespan independently of calorie restriction.

 

That is obviously just the tip of the iceberg when it comes to the subject of cold exposure and its interactions with CR, a topic on which whole books could be written ☺.

 

To its credit, the CR Wikipedia page ends with a pretty cogent cautionary critique:

 

The concept that caloric restriction universally prolongs longevity has been contested. Increased longevity is measured only relative to control animals, but a review of the evidence indicates that the lives of these control animals are artificially shortened by weight-gain from unnatural ad libitum feeding in the laboratory.

 

That's about the most accurate and intelligent thing on the whole page, and a good way to end it.

 

Is the CR Wikipedia page perfect? No. Far from it. Should I edit it? Yeah, right. That's all I need - to get into another pissing match with a bunch rabid Wikepedia editors who also happen to be CR fanatics, with their own little fiefdom and who have been tweaking that page for years.  No thanks. I'll pass.

 

It doesn't matter anyway. The information is out there, and in here (i.e. contained in these forums). 

 

Someday, when Google's AI gets smart enough, it will crawl and slurp it's way through these forums, Nameless' blog post, the old email-list archive (which thankfully is largely available in mine and other old-timer's Gmail archives, and in publicly accessible (but alas not searchable) caches of the email-list tar file...), and especially the millions of pages of original research on CR and related topics available to it via free via Pubmed, and pirated (for now) via sci-hub. It will gather all the data together, parse through it in a couple nanoseconds, cogitate over it for a few more, and then spit out the definitive Wikipedia page on CR. 

 

That may be really useful. It may enable some good Cosplay fun, and be a real lifesaver for the 5 or 6 CRON-O-Amish hold-outs still clinging desperately to meat bodies and who want to keep them around for a few more years... Not unlike those 100+ year-old Model-T automobiles Aubrey blabbers about, whose owners obsessively tinker with, never drive very far for fear of damaging them in an accident or wearing out their parts, and that, in the end, really suck as a mode of transportation...

 

This Ultimate CR Wikipedia page will also serve as ground truth for some future, post-human psychosocial-history graduate student, who will inevitably run thousands of ancestor simulations of folks like us, and wonder:

 

"What the #$%&*@ were they thinking with that whole CR thing?"

 

Hmmm... Makes one stop to wonder... If you, dear reader, are such a wonderful wonder-filled person, see #5 here and join the conversation.

 

Now Gordo, please my friend, I'm begging you to stop pushing my buttons on this whole CR thing. Frankly, I'm sick of beating a dead horse sacred cow. 

 

In fact, Please leave me alone about health and longevity topics too. I've got my diet, supplement regime, and lifestyle dialed in for the long haul, just like I want them.  I don't want to dwell on this stuff anymore. I want to turn over a new leaf, and get on with the things that are really important!

 

Thanks for letting me vent...

 

--Dean

 

-------

[1] Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R.Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318-21. doi: 10.1038/nature11432. [Epub ahead of print] PubMed PMID: 22932268.

[AlPater]

I searched and looked at the results for "Your search for the term colman beasley kemnitz returned 2 results" and neither seemed to have the below paper.

 

So I searched and "No results found for '24691430'."

 

I could be mistaken, but I assume that the below paper has not been introduced before, but even if it has, it probably could be discussed here and included for future reference, in case it has been discussed without its PMID #.

Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys.
Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM.
Nat Commun. 2014 Apr 1;5:3557. doi: 10.1038/ncomms4557.
PMID: 24691430
Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988801/

Abstract

Caloric restriction (CR) without malnutrition increases longevity and delays the onset of age-associated disorders in short-lived species, from unicellular organisms to laboratory mice and rats. The value of CR as a tool to understand human ageing relies on translatability of CR's effects in primates. Here we show that CR significantly improves age-related and all-cause survival in monkeys on a long-term ~30% restricted diet since young adulthood. These data contrast with observations in the 2012 NIA intramural study report, where a difference in survival was not detected between control-fed and CR monkeys. A comparison of body weight of control animals from both studies with each other, and against data collected in a multi-centred relational database of primate ageing, suggests that the NIA control monkeys were effectively undergoing CR. Our data indicate that the benefits of CR on ageing are conserved in primates.

Edited September 12, 2016 by AlPater

[mikeccolella]

Oh well, here we go again!!!

[Matt]

Did anyone at the last conference have some updates about the rhesus monkey studies? 

CR in rhesus monkeys didn't do as well as we hoped, but I wouldn't completely dismiss the idea of CR working, at least in some people. There were some confusing results from the studies in that they both never responded to calorie restriction in the way we expected, so take that for what it's worth. It'd be interesting if we could tell what the 'signal' is for CR having an effect on aging, because right now, despite all the research gone into CR, it doesn't seem like researchers have fully grasped why CR actually working in some but not others, whilst exhibiting similar changes in biomarkers on either genetic, biological or physiological level.

 

In the NIA paper, didn't they mention that:

 

4 monkeys in the calorie restricted group have lived beyond 40 years and only 1 control monkey? 

 

and

 

Researchers analysed data on lifespan of 3264 rhesus monkeys, and only two 40-year old monkeys have ever been documented
 

I know we've seen this before, like in rats where they've been restricted a lot, and many younger rats die, but there is quite a few at the end who live much longer than normal.  Same happened in wild-type mouse model where there was no real increase in average, but significant increase in maximum lifespan.

 

At this point I can't imagine going off CR, but I have eased up a little (mostly because I just want to look a bit better); but I'm starting to realise now more than ever that CR may be quite weak, and we really need to focus on things like SENS, AI, and other things which will really impact our chances of having a very long life...

 

Lastly, I still can't help notice that almost everyone I knew from school seems to be far older than me. I meet people all the time and they say I'm pretty much the same as when I was in high school or college and I'm now almost 32 years old. I started eating healthily when I was 18, and serious CR at 20. Based on how I feel and the difference I see (and everyone else who knows me), it would seem crazy to go off CR. Not sure if looking younger means living longer, but I like it. = ) 

Edited September 13, 2016 by Matt

[Matt]

That reminds me, you should edit the wikipedia page on calorie restriction, it seems quite dated.

 

Wow, one line on human CR studies? The CR article is quite bad, go edit it = 0

 

"Critique[edit]

The concept that caloric restriction universally prolongs longevity has been contested. Increased longevity is measured only relative to control animals, but a review of the evidence indicates that the lives of these control animals are artificially shortened by weight-gain from unnatural ad libitum feeding in the laboratory.

 

I haven't read this review, but CR has been quite extreme in some experiments, almost to the point of starvation with better results than mildly or moderately restricted animals who were also very lean. 

 

off topic: If anyone wants to edit it, you couldn't slip my CR page link into the wiki article could you? :p

 

Jk 

 

 

Edited September 14, 2016 by Matt

[Gordo]

Matt, have you read Michael's analysis?  I'm sure someone will correct me if I'm "off", but the bottom line is that that NIA study was closest to testing a healthy diet + obesity avoidance (hence the title of this thread) vs. CR+healthy diet + obesity avoidance, and the end result was that CR had no special, statistically significant advantage.  The Wisconsin study showed that CR + a "not so great diet" beats a "not so great diet" without CR (which is no surprise).  This is akin to the recent CALERIE study where they looked at overweight people doing mild CR (I don't think there were any surprises).

 

When you compare yourself to your peers - how many of those peers have a "healthy obesity avoiding diet and lifestyle"?  Since people seem to get really confused about what a healthy diet is, lets just stick to the only diet scientifically proven to prevent and reverse heart disease (the number one killer).  OK, if there are any left, are these peers measuring their biomarkers of health and ensuring they get adequate micro nutrients, phytochemicals and immune boosting foods? How about sleep and exercise?  

 

Did their lunch today look anything like mine?

(from left to right: King oyster mushrooms, mixed nuts, mango, beets, red onion, peach, sweet bell pepper, spinach, kale, chia seed, flax seed, spices, fresh turmeric root, black pepper, enoki mushrooms, extra virgin olive oil, natto, avocado, cauliflower, lime, green lentils, tomato, barley, oats, blueberries, pomegranate, sweet potato)

 

Finally, if there's still anyone left on your list - have they been doing this as long as you have?

 

I noticed even in one of Fontana's later CR related papers he speculates that perhaps it isn't the calories, but the diet (specifically he mentioned high fiber and high phytonutrients) that were responsible for the improved biomarkers of health he observed.

 

In short - there is no evidence that CR will beat a healthy obesity avoiding diet and lifestyle in humans, and plenty of anecdotal evidence that it won't.

Edited September 15, 2016 by Gordo

[Matt]

Yup, I've read Michael's post. I also wrote 5000 words on it, but Michael did a better job and covered a lot more. There is a lot of interpretation here though, we can try to explain it but to he honest, the rhesus monkey studies are still hard to ignore, even for myself, yet I carry on doing calorie restriction because it is still, today, the best thing available to us. It doesn't feel like much of a gamble because after such a long time doing this, it's pretty easy. Maybe I'm not starving myself enough? :p 

 

I'd have to also refresh my memory about the studies, but from what I remember, the groups difference in caloric intake decreased over time, meaning the level of restriction was not as was intended. Also, some bizarre results when it came to things like triglycerides in female monkeys which were much higher than the control monkeys. We don't see this in humans. And since the monkeys' were on a healthy diet, we should've expected to see a similar response to humans. 

 

I guess then that the Wisconsin monkeys represent sedentary westerners on a bad diet then? So we should see a big difference and outlive most of our peers? or no?

I'm talking about 99% of them, whether they are skinny or fat. But sure, very few if any eat the kind of diet I do. So what you're saying is that it's not the CR per se, but the fact I eat very healthily? But there's no way to prove this either way haha.

 

I like to compare how my sister is ageing. She is around the same age, 2 years younger, lean (BMI 19), okay diet. It's been said a lot that I look much younger than her. People think I am her younger brother... But there is not a huge difference in how we look compared to my peers. She has thicker hair than me though, ufff :p 

 

Looking back at family photos, close relatives, I still look considerably younger than all of them. But again, could be just the quality of my diet, not how many calories. 

 

So yeah, there is no evidence in humans that a CR + Good diet will beat out a good diet. I haven't seen Fontana's latest paper... Not sure I could access it. 

 

Nice food by the way! Looks delicious :D

Edited September 15, 2016 by Matt

[Gordo]

"So we should see a big difference and outlive most of our peers? or no?"

Probably, but it would also help if you were locked up in a cage in a clean lab, protected from infectious diseases or falling and breaking a bone  ;)

 

"So what you're saying is that it's not the CR per se, but the fact I eat very healthily? But there's no way to prove this either way haha."

Hard to prove, for sure.  Will you outlive your peers on this forum for example, who have a healthy diet and exercise but don't do severe CR?  Not likely in my opinion but only time will tell... keep an eye on the serious CR folks who have done it for decades and are currently >70 years old.  Do they have bone loss problems (osteoporosis)?  Sarcopenia?  Mental issues?  Blood sugar control difficulty?  Slow recovery from illness?  The anecdotal reports I've seen and read are not good.  CR Pioneer Roy Walford died at age 79, did CR kill him? Maybe.  Could severe CR reduce or eliminate your ability to benefit from CE? Probably.

[The Observer]

Matt, you and I are the same, down to the teeth. Blood brothers, perhaps.   Reading your experiences regarding your peers and what others say about you, it's like reading my own words. I just turned 38 recently. On 22nd of July (Hi Gordo  ). My brother is 27 and we look about the same age, but certainly no more than 3-5 years apart.  I had a BMI of about 18 for most of my life and I was always the smallest. 

 

Having no wrinkles I also did a quick research on skin aging, because I recently ran into one of my classmates from high school and his facial skin must have looked ~20 years older than mine. I guess he is on the opposite extreme of the spectrum. Info sites like this one: http://www.womens-health-advice.com/skin-care-questions/aging-first-signs.html

 

... which also suggest I should be in late twenties or ~30, since I noticed my skin getting a bit dry on the forehead only in the last 2 years or so. I do avoid sunlight exposure more than my brother, but then again he exercises a lot more.

 

Now visiting this forum the last couple of months I came to the conclusion that CR probably does not work, so I don't know what to think now. 

 

After all the research, is anecdotal evidence really all we are left with to cling our hopes on? 

Edited September 18, 2016 by The Observer

[Matt]

I think the evidence that CR killed Roy Walford earlier is pretty weak; and it has been discussed many times on the lists over the years.  I don't imagine we'd see more Sarcopenia in humans on CR. Even the in the rhesus monkey studies there was some good results showing that CR preserved muscle and function (if I remember correctly), as it does in rodents. 

Mental issues? Any evidence that it's higher in people who are on CRON? 

The two that really concern me, and what we're probably most at risk for is infection and osteop

 

Blood sugar control difficulty? Are you referring to the Glucose tolerance tests done on people doing CR? What about this? Under normal circumstances eating our plants, beans, and fruits, this probably does happen? I've seen people report great results, and very low fasting glucose levels. 

[Matt]

That's great! :D

 

Well, you know that CR slows the appearance of aging in animals and monkeys, so why not humans? :p There was a study done a few years ago on twins looking at perceived age, and the twin who was perceived as looking older was more likely to die first. I guess in humans though there are other variables, one being sun exposure.
 

I have a friend who is probably the only person who also looks relatively young for his age, maybe a bit older than me, but doing well. His BMI is always around 19 and he's been lean all of his life and has a small body frame too. So, I think one important thing is to stay lean and remain lean - unless you're Jared Leto. :p 

 

None of us can say for certain whether or not it will work, but we do have good evidence for disease prevention. For me personally, it doesn't feel like much of an option when there is nothing really out there which comes close to CR in terms of evidence. Is it a gamble? maybe... But I placed that bet in 2005 when I started more serious CR, and I have no regrets about it either. 

 

Another anecdote: Masako Mizutani looks great still and she eats a CR-like diet. Quite healthy, and really thin. She doesn't specifically say she does CR, but says she eats lightly. Last time I read her BMI was around 17. 

 

Hmmm One reason for dry skin could a be decline in testosterone levels?

 

I'm going on the human studies which show good results in humans for disease prevention. For example, autoimmune diseases tend to be prevalent on my mum's side (mum has lupus), so I think about things like that when I do CR. I want the longevity benefits, but I think both short term and long term. I want to be in the best possible condition for when something like SENS is achieved.  I still believe i'll make it to 100 without help of any advanced medicine... which is 15 years longer than my grandparents lived (most died of lung caner from smoking). 

 

So, we could just keep going around in circles. No one can really answer whether or not obesity avoidance with a good diet is enough. I mean, it'd be interesting to compare people on CR to raw foodists who are less restricted. I know we have similar results when it comes to blood pressure, glucose, insulin etc..  what about gene expression? thyroid hormone levels, testosterone / estrogen among other markers. If they are not pointing significantly different, then maybe CR does offer the potential for more life. 

Edited September 19, 2016 by Matt

[Gordo]

Don't you guys remember not all that long ago when longevity researchers were all excited about Laron syndrome and what it might imply? Valter Longo practically made a career out of it.  An 18 year old that looks like a 1st grader?  YES WE CAN:

(Jannick Castillo, who has Laron Syndrome, was 18 years old in the above picture)

 

You can search the popular press about it, there are countless articles and mainstream media coverage.  Hate to break the news to you though, but that bubble didn't last long, and has since burst.  These low IGF-1 folks do not have special longevity despite looking decades younger than their biological ages would suggest.  Listening to Longo dodge this question in interviews was always entertaining, his answer was usually something like "Uhhh, we don't really know how long they could live since they die from a lot of accidents".  Anyway, my guess is that the same likely applies to anyone with low IGF-1 (natural or otherwise).  There are definitely some benefits to low IGF-1, looking younger is one of them, but there are also downsides as has been discussed on this forum.

Edited September 19, 2016 by Gordo

[Matt]

I'm already aware of this Syndrome, and I've also wondered why they don't seem to live longer. Apparently the deaths are mainly from accidents or are alcohol-related. They are also really obese.

 

"The effect on life span may have been obscured in this study by the unusually high number of accidents and alcohol-related deaths seen in the Laron subjects." Article

 

Most of them seem to be obese, and they don't seem to look especially young either. I don't think Jannick looks exactly like a kid. Normally the dimensions of our face change and grow and age -- these help determine perceived age. I'm sure it has with him as well, but on a smaller level, which makes it more confusing. There are sutble signs that he's older. News report with Jannick

 

The older people with Laron syndrome don't look younger than their age do they?

 

Reduced IGF-1 in humans has been found to be one factor in extreme longevity though, and predicts survival in those with exceptional longevity. And that's not the only study either. 

 

And so what of the fact that these people do not live longer? IGF-1 is merely one part the cog or system in ageing where it may protect you from some diseases if you reduce it, whilst potentially raising the risk of other problems. I don't see that being controversial? It just means that we ought to pay attention to the things that might kill us more frequently. 

People with partially reduced IGF-1 signalling may have more of a balance between the pros and cons, and not need to be as cautious about the negative side of either extreme (or normal levels).

 

With regards to looking younger: I'm just pointing out that you should expect this to happen. It's just part of ageing more slowly. Sounds like I'm stating the obvious here. :) It's not as if I am saying looking younger will cause people to live longer, but it's common in those who do live longer. And I'm really   happy with the results after doing CR for a long time.

 

I'm still fairly optimistic, and still think I would get at least 15-20 years from CRON. I would hope that near 2100 we would have a cure for aging!   I would be 116! scary =) 

Edited September 19, 2016 by Matt

[Gordo]

OK, but you haven't built the case for severe CR at all.  The best way to lower IGF-1 isn't via CR, in fact CR in and of itself is not even a good way to lower IGF-1.

 

 

• https://youtu.be/hcIkhffzrkk

   Daily Video /  October 1st, 2012
  Protein Intake & IGF-1 Production

  Animal protein consumption triggers the release of the cancer-promoting growth hormone IGF-1.

• https://youtu.be/BqkwPL0mSGw

   Daily Video /  September 28th, 2012
  How Plant-Based to Lower IGF-1?

  Those eating vegan had significantly lower IGF-1 levels and higher IGF-binding proteins than those just eating vegetarian, suggesting that the more plant-based one's diet becomes, the lower one's risk of fueling growth hormone-dependent cancer growth.

• https://youtu.be/ayuVb9-nFVo

   Daily Video /  September 25th, 2012
  IGF-1 as One-Stop Cancer Shop

  Insulin-like growth factor (IGF-1) is a natural human growth hormone instrumental in normal growth during childhood, but in adulthood can promote abnormal growth—the proliferation, spread (metastasis), and invasion of cancer.

• https://youtu.be/Q7AvgBgI8f4

   Daily Video /  November 19th, 2014
  Caloric Restriction vs. Plant-Based Diets

  What is the best strategy to lower the level of the cancer-promoting growth hormone IGF-1?

 

To quote Dean as it relates to the last one:

 

In his weekly newsletter out today, Dr. Greger did a story on Calorie Restriction vs. Plant-Based Diets which highlighted results from two of Luigi's studies on us (PMIDs 18843793 and 17158430). He discusses the important health and lifespan benefits of keeping IGF-1 low, and uses Luigi's studies to (allegedly) argue that it is a plant-based diet, and not the reduced calories, that results in low IGF-1. 

 

I didn't remember this part of Luigi's study, which Dr. Greger used as evidence that it is the plant-based diet rather than CR that drops IGF-1:

 

Therefore, we conducted additional studies to evaluate the importance of long-term protein intake in modulating serum IGF-1 concentration in humans. In one study, we evaluated serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio in 28 vegans who had been consuming a moderately protein-restricted (PR) diet (0.76 g kg−1 per day; ~10% of intake from protein) for ~5 years age-matched with 28 members of the Calorie Restriction Society who consume a high-protein diet (1.73 g kg−1 per day; ~24% of energy intake from protein) (Table 3). Protein intake was significantly lower in the moderately PR group than in the CR group, while energy intake tended to be higher (Table 3). Both serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio were significantly lower in the moderately PR diet group than in the severe CR diet group, whereas fasting insulin and C-reactive protein were similarly low in the moderately low-protein vegan and CR groups (Fig. 2), as previously reported in a smaller group of raw food vegans (Fontana et al., 2006a, 2007a). This effect of a moderate protein restriction is independent of body weight and body fat content, as serum total and free IGF-1 concentrations were lower in the moderately PR group than in the severe CR high-protein diet group, despite the PR groups’ higher body weight, BMI and body fat content (Table 4).

 

Dr. Greger's summary of these results is pretty accurate:

 

Only the vegan group got a significant drop in IGF-1. These findings demonstrate that, unlike in rodents, long-term severe caloric restriction in humans does not reduce the level of this cancer-promoting hormone. It’s not how many calories we eat, but the protein intake that may be the key determinant of circulating IGF-1 levels in humans, and so reduced protein intake may become an important component of anti-cancer and anti-aging dietary interventions.

 

But once again Dr. Greger's agenda (bless his heart) shines through a bit. Given the title of this article ("Calorie Restriction vs. Plant-Based Diets") he seems to be hoping his readers will equate "plant-based" or "vegan" with "low protein". While generally this is the case, the two don't necessarily go together. It's possible to eat a high protein vegan diet (e.g. with concentrated soy products, vegan protein isolates etc), just as it's possible to keep protein low on a diet that includes animal products (not so easy, but ketogenic diet folks do it w/ lots of butter etc.).

 

My personal data might seem to support Dr. Greger's conjecture. Since I eat a lot of calories, I also eat a lot of protein (96g/day, or 2x the RDI). But since I'm vegan, all of it plant-based and so my IGF-1 remains low (83, RR 61-200). In fact my IGF-1 now is less than half what it was when Luigi tested me in 11/2002, when (as I recall) I believe I was eating a lacto-ovo-(maybe pesco...)-vegetarian diet, with many fewer calories, more animal products, and about the same total protein. But don't hold me to that - since that was around that time I went vegan IIRC. Unfortunately I don't have records going back that far (except blood tests). Tom, anything in the archives?

 

Regardless, my example is not very definitive anyways, because despite my high calorie and relatively high (plant-based) protein diet, I'm maintaining a net calorie deficit, which may explain my low IGF-1 level, independent of protein amount or source.

 

So maybe it is low animal protein and not just low protein that makes the difference. But I don't think Dr. Greger makes a very good case for this hypothesis in his article, to put it mildly.

Edited September 20, 2016 by Gordo

[kpfleger]

One of the points that started this thread is that controls in many CR studies were very unhealthy diets/lifestyles, so CR results looked inflated vs. using a healthy baseline. It is important to emphasize that this is a much wider issue. It's a *huge* systematic problem across all of health-science & medicine that calls into question just how valuable a wide range of seemingly scientifically-backed practices/interventions really are. Many may only be ways to make up for unhealthy habits, better thought of as treatments for a bad lifestyle rather than treatments for whatever they are supposedly for.

 

For example, most of the promising-looking data on fasting or IF is relative to unhealthiness (eg average American humans). How much value is there to Longo's IF approach that generated so much hype recently relative to typical healthy vegan diets that have so many proponents? I would be surprised if there weren't similar issues with the rodent IF results. This is also a problem for much of anti-aging science. The problems Dean described in the 1st post of CR's benefits looking inflated due to genetically in-bred rodents, lab conditions, etc. plague other interventions besides CR, such as drugs like Rapamycin. If you divide by a smaller number, it's much easier to get a bigger result!

 

I'm not sure the best way to deal with this problem in science based on rodents and other short-lived species, but to get an idea of the magnitude of this problem in human studies, consider the stats on just how dominant unhealthy lifestyle is, which I found to be a bit of a splash of cold-water when I read them in Novick's triage good/bad/ugly post:

Depending on the source and the exact list of most important 4-7 lifestyle factors, only:
Only 2.8% of US adults did 4 of 4 ["Healthy Lifestyle Characteristics..." (2005) ARCH INTERN MED/VOL 165]
Only 4% did 5 of 5 [Circulation. 2006 Jul 11;114(2):160-7. "Healthy lifestyle factors..."]
Only 3.1% did 5 of 5 [stampfer et al (2000) "Primary prevention of coronary ..." N Engl J Med. 343: 16–22]
1% of people did 6 of 7 [AHA criteria for cardiovascular health]

Across all of these the top factors were roughly the same, no smoking, BMI<25, exercise, healthy food. And across all of these it's not only doing all top 4-6 things that is hard. Even doing only 2 of the top 5 is hard (eg, a third or less of people). These are the pools of people being randomized into treatment and control in almost all human studies. What are we supposed to take away from the results we then get?

 

As for choosing which healthy diet is best, I think there is a reasonable chance that DNA methylation or maybe measurement of counts of senescent cells or some other advance will provide large quantities of accurate data within a decade or two to meaningfully judge CRON vs. all the other types of healthy, mostly-plant-based diets.

As an aside, let's see, the main competitors seem to be:
(a) CRON (aka restrict total calories) [Fuhrman’s maximize (micro)nutrients/calories philosophically goes in this bucket too, though the communities don't overlap much and there is possibly a difference in extremes, at least on average],
(b) PRON (ie protein restriction),
© low-fat (<10%) whole-foods vegan such as Ornish, McDougall, Esselstyn (ie fat restriction),
(d) (mostly) vegan ketogenic with minimal processed foods (ie carb restriction),
(e) raw (mostly) vegan.

But already the evidence on hand seems very suggestive that any differences between any of the above are small relative to any of them vs. most of the population i.e. standard American/western diet/lifestyle. primarily because the latter is just *so* bad.
 

-Karl

 

[Mechanism]

Edited

Edited July 19, 2020 by Mechanism

[Sthira]

I like the M.Pollan advice and follow it, too. But correct me if I'm wrong here: I loosely view that all food (even the very peak of the healthiest, most nutritionally powered of the leafiest of leafies) is detrimental to life extension. Like breathing, right, eat and breathe if we must to stay alive; but these required necessities are killing us. And we ain't got much choice in the matter yet.

Edited October 25, 2016 by Sthira

[Mechanism]

Edited

Edited July 19, 2020 by Mechanism

[Sthira]

Actually I've grown to enjoy fasting more frequently. It's a challenge to body and brain, it's a controlled form of stress, it's relatively easy, it's free, in fact it saves me money on expensive beans and greens and wow nuts and seeds are expensive due to the California droughts.

 

But I don't know how much fasting is too much fasting just as when I was seriously practicing CR I never quite could grasp how much CR was too much CR. And I tend to go overboard on aspects of behavior I consider healthy, yet I'm not clear when something like fasting becomes too much of a good thing. So for now I'm going on BMI (I refuse to go down past 18 -- which is about where I am now) and subjective feeling. How do I feel after doing so much fasting? Sometimes great, sometimes miserable, sometimes neutral. I'll soon get some blood markers tested to find out a few more clues -- although I don't think testing expensive blood markers leads to that much increased knowledge.

 

What is extreme? Clearly judging by typical Americans I'm way past extreme to the point where I don't even tell anyone I'm fasting anymore. There's literally zero support off-line for what I'm doing, and I found this true for practicing calorie restriction, too.

 

As to the question of this thread, I think the answer is yes, a CR diet will "beat" a healthy obesity avoiding diet. But I'm practicing for now fasting, which is much more fun and sustainable for me than calorie restriction.

[kpfleger]

I like the M.Pollan advice and follow it, too. But correct me if I'm wrong here: I loosely view that all food (even the very peak of the healthiest, most nutritionally powered of the leafiest of leafies) is detrimental to life extension. Like breathing, right, eat and breathe if we must to stay alive; but these required necessities are killing us. And we ain't got much choice in the matter yet.

 

I had been planning to mention some possible justifications of CR despite what I said earlier. Thanks for the lead-in. There does seem to be a lot of evidence that much of aging is damage of some sort that builds up as an inevitable consequence of metabolism (see for example Ending Aging, which I think provides the easiest-to-read treatment that really delves into this deeply, though it isn't only Aubrey's camp making these claims). Based on that view, one possible justification of CR(ON) even if it is unlikely by itself to result in many additional healthy years past other health-promoting lifestyles that don't reduce metabolism as much could be a belief that SENS like damage-removal technologies (senolytics, etc.) will come along in the future but only slowly and with imperfect effectiveness initially, such that those with less damage may achieve "escape velocity" while others don't. Even if expected remaining lifespan might be similar without those treatments. It's impossible to know how likely this is at this point though.

 

Of course this line of reasoning also requires a belief that the alternative baseline healthy lifestyles achieve their benefits in ways other than also reducing metabolism and its negative consequence of damage accumulation. We already know a lot about some of the similarities in ways the various healthy diets affect various metabolic pathways though and certainly many aspects overlap with CR's changes, though of course there re differences. As new technologies come along to measure the various forms of damage accumulation we might get a better sense of all of this.

 

 

A second possible justification of CR even if it currently had equal expected benefit vs. these other baseline healthy diets would be if it really was better in some ways but also worse in others due to negative consequences/risks (such as possibly increased infection risk, bone risk, insulin resistance, etc.), and if in the future changes mitigated/cured the CR negatives faster than the things CR helps with (relative to the alternatives). For example, a universal flu vaccine may be on the horizon and would reduce infectious risk, advances in continuous glucose monitoring might mitigate the insulin resistance risk, etc. When the profile of advantages/risks of 2 different healthy lifestyles don't align perfectly, betting on which disadvantages future medical advances will deal with first seems unfortunately to be a hard game.

 

In general, I'd bet on the advances that help with the problems the majority of the population have. Dean pointed out that the expected lifespans of high-BMI have been increasing faster than those of low-BMI and I think this is largely because more people have those higher BMIs so the corresponding problems get more research funds (both from government and from business). CR problems don't in general line up super-well with majority-of-population unfortunately for CR.

[Mechanism]

Edited

Edited July 19, 2020 by Mechanism

[Gordo]

"But I'm practicing for now fasting, which is much more fun and sustainable for me than calorie restriction. "

 

You have an 18 BMI and do extensive, repeated, water only fasts, and yet you think you are not restricting calories?

 

"I think the answer is yes, a CR diet will "beat" a healthy obesity avoiding diet"

 

Based on what scientific evidence?

 

"I loosely view that all food (even the very peak of the healthiest, most nutritionally powered of the leafiest of leafies) is detrimental to life extension"

 

So by this theory Dean should be "aging"/deteriorating at a very high rate, right?  Again, do you have some scientific evidence?  Do we even have anecdotal evidence from Dean?

[Dean Pomerleau]

Gordo,

 

So by this theory Dean should be "aging"/deteriorating at a very high rate, right?  Again, do you have some scientific evidence?  Do we even have anecdotal evidence from Dean?

 

Regarding Q1: Hope not!

 

Regarding Q3: As far as I can tell, no, but as of now, estimating one's rate of aging is an inexact science and pretty subjective.

 

--Dean

[Gordo]

estimating one's rate of aging is an inexact science and pretty subjective.

 

--Dean

 

I'm wondering if it might be useful to see your (and others') heart rate variability trending over time?  Then again that might be completely unreliable due to CE practice (not to mention all the nuances of measuring it in the first place: position, timing, immune system activity, circadian rhythm, breathing, etc)

[Sthira]

 

 

"But I'm practicing for now fasting, which is much more fun and sustainable for me than calorie restriction. "

You have an 18 BMI and do extensive, repeated, water only fasts, and yet you think you are not restricting calories?

Well, yeah, I guess since you put it that way, you're right. Obviously zero calories for several days at a time is restricting calories. I may be calorie restricting as evident by some overall decrease. Um, so, I guess my definition of CR is that seemingly very strict one I gleaned from Michael Rae, which I understand as: if I'm not eating consistently, daily under my BMR (by some percentage 5%, 10%, whatever) then I'm probably not practicing formal CR. Maybe this definition is flawed, and the whole "calories calories calories..." idea is flawed, as Dean eloquently hammers.

 

I try not to let BMI fall beneath 18 (although I realize BMI probably isn't a good CR indicator?) and I admit this is mostly for professional reasons because I just end up looking too freaky. Although appearing grossly skeletal during Halloween has its money-making opportunities for sure: boo.

 

 

 

"I think the answer is yes, a CR diet will "beat" a healthy obesity avoiding diet"

Based on what scientific evidence?

Well, I suppose there is no scientific evidence so this is just a hunch, an opinion, a self-experiment. But as Saul posted, and I find compelling: since CR appears to "work" for such a wide range of creatures beyond us, why wouldn't it work for us, too? That's of course some logical fallacy. And I may be balancing that fallacy upon another: precious few studies in people have even been performed, so lack of evidence doesn't mean it doesn't work (extend lifespan). Neither does it mean it works -- here's my educated guessing (which remains in suspension) based on preponderance. Maybe we've just not yet discovered that it works in people because the studies are just too hard for scientists to accomplish? Perhaps computer models (like climatology models) may point a gnarly finger at the moon?

 

 

"I loosely view that all food (even the very peak of the healthiest, most nutritionally powered of the leafiest of leafies) is detrimental to life extension"

So by this theory Dean should be "aging"/deteriorating at a very high rate, right? Again, do you have some scientific evidence? Do we even have anecdotal evidence from Dean?

Yes, I'd say that Dean is aging right on schedule along with everyone else. His rate of aging might be slower, or maybe not, who's to say? My point was all food is killing us, all breathing is killing us, it's just that some food and some breathing might be killing us less quickly than others. And that's of course another wild generalization. Edited October 27, 2016 by Sthira